Modern transfusion regimens designed to maintain the hemoglobin concentration above 11 g/dl are capable of preventing the primary manifestations of thalassemia major, but ultimately result in iron-overload. The development of subcutaneous deferoxamine therapy has made the achievement of iron balance possible, but important questions concerning the long-term clinical effects of such therapy on cardiac and endocrine function remain unanswered; the factors which influence the variability of response to deferoxamine have also not been fully elucidated. During the past two years, the technology has been developed to prepare young red cells for transfusion from ordinary blood bank units. This technology may result in a further reduction in the rates of iron-loading. This proposal will combine the resources of a group of investigators who have a long-standing interest in the improved management of thalassemia major. A clinical trial will be performed to assess "in vivo" the effectiveness of transfusion of young red cells. These will be prepared initially using the IBM cell washer, while a new and inexpensive single-half technique is developed. The effect on cardiac function of decreasing the oxygen affinity of hemoglobin will be assessed. The efficacy of oral Deferoxamine on fecal Fe excretion and of its administration at high-dose on cardiac function will be evaluated. Cardiopulmonary function of the patients will be evaluated both in the steady state and under stress and will be correlated with the patients iron balance state and the effects of the proposed improvements in management.